Molecular basis of the CRAC channel

Ca2+ release-activated Ca2+ (CRAC) channels, located in the plasma membrane, are opened upon release of Ca2+ from intracellular stores, permitting Ca2+ entry and sustained [Ca2+]i signaling that replenishes the store in numerous cell types. This mechanism is particularly important in T lymphocytes of the immune system, providing the missing link in the signal transduction cascade that is initiated by T cell receptor engagement and leads to altered expression of genes that results ultimately in the production of cytokines and cell proliferation. In the past three years, RNA interference screens together with over-expression and site-directed mutagenesis have identified the triggering molecule (Stim) that links store depletion to CRAC channel-mediated Ca2+ influx and the pore subunit (Orai) of the CRAC channel that allows highly selective entry of Ca2+ ions into cells.